PSD-95 Protein
Overview
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">PSD-95 Protein</th>
</tr>
<tr>
<td class="label">Protein Symbol</td>
<td>PSD-95 (DLG4)</td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>Postsynaptic Density Protein 95</td>
</tr>
<tr>
<td class="label">NCBI Protein ID</td>
<td>NP_001359.2</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q12959</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>95.4 kDa</td>
</tr>
<tr>
<td class="label">Amino Acids</td>
<td>724</td>
</tr>
<tr>
<td class="label">Domain</td>
<td>Positions</td>
</tr>
<tr>
<td class="label">PDZ1-3</td>
<td>1-300</td>
</tr>
<tr>
<td class="label">SH3</td>
<td>400-500</td>
</tr>
<tr>
<td class="label">GK</td>
<td>500-600</td>
</tr>
<tr>
<td class="label">C-terminal</td>
<td>600-724</td>
</tr>
<tr>
<td class="label">Region</td>
<td>Expression</td>
</tr>
<tr>
<td class="label">[Hippocampus](/brain-regions/hippocampus)</td>
<td>Very High</td>
</tr>
<tr>
<td class="label">[Cortex](/brain-regions/cortex)</td>
<td>High</td>
</tr>
<tr>
<td class="label">Striatum</td>
<td>Moderate</td>
</tr>
<tr>
<td class="label">Cerebellum</td>
<td>Low</td>
</tr>
<tr>
<td class="label">Brainstem</td>
<td>Low</td>
</tr>
</table>
Psd 95 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Introduction
Psd 95 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@kim2001]
The DLG4 gene (Discs Large Homolog 4) encodes PSD-95 (Postsynaptic Density Protein 95), a major scaffolding protein at excitatory synapses. PSD-95 is critical for synaptic structure, function, and plasticity, and is implicated in neurodegenerative diseases. [@funke2011]
Protein Overview
Normal Function
PSD-95 is a core postsynaptic density protein:
- Synaptic scaffolding: Organizes postsynaptic machinery
- AMPA receptor anchoring: Regulates synaptic transmission
- [NMDA](/entities/nmda-receptor) receptor clustering: Essential for synaptic plasticity
- Signaling complexes: Gathers signaling proteins
- Synaptic plasticity: Learning and memory mechanisms
Molecular Mechanism
Domain Architecture
PSD-95 contains multiple domains:
Key Interactions
PSD-95 scaffolds synaptic proteins:
AMPA receptors: GluA1-4 subunits via stargazin
NMDA receptors: NR2A/B subunits
K+ channels: Kv1.x channel anchoring
Signaling enzymes: nNOS, CaMKII
Other scaffolds: SAP97, SAP90Synaptic Organization
PSD-95 organizes the postsynaptic density:
- Clusters neurotransmitter receptors
- Links to actin cytoskeleton
- Organizes signaling complexes
- Maintains synaptic structure
Brain Expression
PSD-95 expression in brain:
Expression is neuronal-specific, concentrated in excitatory synapses.
Disease Associations
Alzheimer's Disease
- PSD-95 loss in AD brains
- Synaptic dysfunction mechanism
- Correlates with cognitive decline
- Therapeutic: Restore synaptic proteins
Parkinson's Disease
- Altered in substantia nigra
- Dopaminergic synapse changes
- Levodopa-induced modifications
- Therapeutic target
Huntington's Disease
- PSD-95 dysregulation
- Synaptic deficits in HD
- Mutant [huntingtin](/proteins/huntingtin-protein) interactions
- Therapeutic potential
ALS
- Motor neuron synapse loss
- PSD-95 alterations
- Therapeutic target
Autism/Schizophrenia
- Genetic associations with DLG4
- Synaptic developmental disorders
- Cognitive dysfunction
Therapeutic Implications
Targeting PSD-95 for therapy:
Stabilizers: Compounds that stabilize PSD-95
Gene therapy: AAV-mediated expression
Peptide mimetics: Functional domains
Modulators: Enhance synaptic plasticityChallenges:
- Complexity of synaptic regulation
- Cell-type specificity
- [Blood-brain barrier](/entities/blood-brain-barrier)
Animal Models
Key findings from models:
- DLG4 knockout mice: Lethal, synaptic defects
- Transgenic overexpression: Enhanced memory
- AD models: PSD-95 restoration studies
- HD models: Synaptic function
Research Directions
Current research focus:
Super-resolution imaging: Synaptic organization
Protein interactions: Network mapping
Therapeutic screening: Small molecules
Biomarkers: PSD-95 in CSFSee Also
- [DLG4 Gene](/proteins/dlg4-protein)
- [Synaptic Dysfunction Pathway](/mechanisms/synaptic-dysfunction)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [NMDA Receptor](/entities/nmda-receptor)
External Links
- [UniProt: DLG4](https://www.uniprot.org/uniprot/Q12959)
- [NCBI: DLG4](https://www.ncbi.nlm.nih.gov/gene/1749)
- [GeneCards: DLG4](https://www.genecards.org/cgi-bin/carddisp.pl?gene=DLG4)
Overview
Psd 95 Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.
Background
The study of Psd 95 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
References
[Sheng M, et al, PDZ domain proteins: scaffolds for signaling complexes (1999)](https://pubmed.ncbi.nlm.nih.gov/10482235/)
[Kim E, et al, PDZ domains in synaptic protein targeting (2001)](https://pubmed.ncbi.nlm.nih.gov/11239451/)
[Funke L, et al, Molecular mechanisms of PSD-95 in neurological disease (2011)](https://pubmed.ncbi.nlm.nih.gov/22048165/)
[Gardoni F, et al, PSD-95 and Alzheimer's disease (2019)](https://pubmed.ncbi.nlm.nih.gov/31498135/)
[Sun T, et al, PSD-95 in synaptic plasticity and neuropsychiatric disorders (2021)](https://pubmed.ncbi.nlm.nih.gov/33420463/)